1887

Abstract

The ability of to acquire iron from the hostile environment of the host is known to be necessary for virulence and appears to be achieved using a similar system to that described for . In , high-affinity iron uptake is dependent upon the acquisition of copper. The authors have previously identified a gene () that encodes a copper transporter. Deletion of this gene results in a mutant strain that grows predominantly as pseudohyphae and displays aberrant morphology in low-copper conditions. This paper demonstrates that invasive growth by is induced by low-copper conditions and that this is augmented in a -null strain. It also shows that deletion of results in defective iron uptake. In , genes that facilitate high-affinity copper uptake are controlled by a copper-sensing transactivator, Mac1p. The authors have now identified a gene () that encodes a copper-sensing transactivator. A -null mutant displays phenotypes similar to those of a -null mutant and has no detectable transcripts in low-copper conditions. It is proposed that high-affinity copper uptake by is necessary for reductive iron uptake and is transcriptionally controlled by Mac1p in a similar manner to that in .

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2004-07-01
2024-03-28
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References

  1. Altschul S. F., Madden T. L., Schaffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. 1997; Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402 [CrossRef]
    [Google Scholar]
  2. Braun B. R., Johnson A. D. 1997; Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science 277:105–109 [CrossRef]
    [Google Scholar]
  3. Church G. M., Gilbert W. 1984; Genomic sequencing. Proc Natl Acad Sci U S A 81:1991–1995 [CrossRef]
    [Google Scholar]
  4. Crichton R. R., Pierre J. L. 2001; Old iron, young copper: from Mars to Venus. Biometals 14:99–112 [CrossRef]
    [Google Scholar]
  5. Dancis A., Haile D., Yuan D. S., Klausner R. D. 1994a; The Saccharomyces cerevisiae copper transport protein (Ctr1p). Biochemical characterization, regulation by copper, and physiologic role in copper uptake. J Biol Chem 269:25660–25667
    [Google Scholar]
  6. Dancis A., Yuan D. S., Haile D., Askwith C., Eide D., Moehle C., Kaplan J., Klausner R. D. 1994b; Molecular characterization of a copper transport protein in S. cerevisiae: an unexpected role for copper in iron transport. Cell 76:393–402 [CrossRef]
    [Google Scholar]
  7. Davis D., Edwards J. E., Mitchell A. P., Ibrahim A. S. Jr 2000a; Candida albicans RIM101 pH response pathway is required for host-pathogen interactions. Infect Immun 68:5953–5959 [CrossRef]
    [Google Scholar]
  8. Davis D., Wilson R. B., Mitchell A. P. 2000b; RIM101-dependent and -independent pathways govern pH responses in Candida albicans. Mol Cell Biol 20:971–978 [CrossRef]
    [Google Scholar]
  9. Dix D. R., Bridgham J. T., Broderius M. A., Byersdorfer C. A., Eide D. J. 1994; The FET4 gene encodes the low affinity Fe(II) transport protein of Saccharomyces cerevisiae. J Biol Chem 269:26092–26099
    [Google Scholar]
  10. Eck R., Hundt S., Hartl A., Roemer E., Kunkel W. 1999; A multicopper oxidase gene from Candida albicans: cloning, characterization and disruption. Microbiology 145:2415–2422
    [Google Scholar]
  11. Eide D. J. 1998; The molecular biology of metal ion transport in Saccharomyces cerevisiae. Annu Rev Nutr 18:441–469 [CrossRef]
    [Google Scholar]
  12. Eide D., Davis-Kaplan S., Jordan I., Sipe D., Kaplan J. 1992; Regulation of iron uptake in Saccharomyces cerevisiae. The ferrireductase and Fe(II) transporter are regulated independently. J Biol Chem 267:20774–20781
    [Google Scholar]
  13. Furst P., Hamer D. 1989; Cooperative activation of a eukaryotic transcription factor: interaction between Cu(I) and yeast ACE1 protein. Proc Natl Acad Sci U S A 86:5267–5271 [CrossRef]
    [Google Scholar]
  14. Gancedo J. M. 2001; Control of pseudohyphae formation in Saccharomyces cerevisiae. FEMS Microbiol Rev 25:107–123 [CrossRef]
    [Google Scholar]
  15. Garcia S., Prado M., Degano R., Dominguez A. 2002; A copper-responsive transcription factor, CRF1, mediates copper and cadmium resistance in Yarrowia lipolytica. J Biol Chem 277:37359–37368 [CrossRef]
    [Google Scholar]
  16. Gillum A. M., Tsay E. Y. H., Kirsch D. R. 1984; Isolation of the Candida albicans gene for orotidine-5′-phosphate decarboxylase by complementation of S. cerevisiae URA3 and E. coli pyrF mutations. Mol Gen Genet 198:179–182 [CrossRef]
    [Google Scholar]
  17. Graden J. A., Winge D. R. 1997; Copper-mediated repression of the activation domain in the yeast Mac1p transcription factor. Proc Natl Acad Sci U S A 94:5550–5555 [CrossRef]
    [Google Scholar]
  18. Gross C., Kelleher M., Iyer V. R., Brown P. O., Winge D. R. 2000; Identification of the copper regulon in Saccharomyces cerevisiae by DNA microarrays. J Biol Chem 275:32310–32316 [CrossRef]
    [Google Scholar]
  19. Halliwell B., Gutteridge J. M. C. 1999 Free Radicals in Biology and Medicine Oxford: Oxford University Press;
  20. Hammacott J. E., Williams P. H., Cashmore A. M. 2000; Candida albicans CFL1 encodes a functional ferric reductase activity that can rescue a Saccharomyces cerevisiae fre1 mutant. Microbiology 146:869–876
    [Google Scholar]
  21. Hassett R., Dix D. R., Eide D. J., Kosman D. J. 2000; The Fe(II) permease Fet4p functions as a low affinity copper transporter and supports normal copper trafficking in Saccharomyces cerevisiae. Biochem J 351:477–484 [CrossRef]
    [Google Scholar]
  22. Heymann P., Ernst J. F., Winkelmann G. 1999; Identification of a fungal triacetylfusarinine C siderophore transport gene (TAF1) in Saccharomyces cerevisiae as a member of the major facilitator superfamily. Biometals 12:301–306 [CrossRef]
    [Google Scholar]
  23. Hu C. J., Bai C., Zheng X. D., Wang Y. M., Wang Y. 2002; Characterization and functional analysis of the siderophore-iron transporter CaArn1p in Candida albicans. J Biol Chem 277:30598–30605 [CrossRef]
    [Google Scholar]
  24. Ish-Horowicz D., Burke J. F. 1981; Rapid and efficient cosmid cloning. Nucleic Acids Res 9:2989–2998 [CrossRef]
    [Google Scholar]
  25. Jensen L. T., Winge D. R. 1998; Identification of a copper-induced intramolecular interaction in the transcription factor Mac1 from Saccharomyces cerevisiae. Embo J 17:5400–5408 [CrossRef]
    [Google Scholar]
  26. Jensen L. T., Posewitz M. C., Srinivasan C., Winge D. R. 1998; Mapping of the DNA binding domain of the copper-responsive transcription factor Mac1 from Saccharomyces cerevisiae. J Biol Chem 273:23805–23811 [CrossRef]
    [Google Scholar]
  27. Jungmann J., Reins H. A., Lee J., Romeo A., Hassett R., Kosman D., Jentsch S. 1993; MAC1, a nuclear regulatory protein related to Cu-dependent transcription factors is involved in Cu/Fe utilization and stress resistance in yeast. Embo J 12:5051–5056
    [Google Scholar]
  28. Kampfenkel K., Kushnir S., Babiychuk E., Inze D., Van Montagu M. 1995; Molecular characterization of a putative Arabidopsis thaliana copper transporter and its yeast homologue. J Biol Chem 270:28479–28486 [CrossRef]
    [Google Scholar]
  29. Keller G., Gross C., Kelleher M., Winge D. R. 2000; Functional independence of the two cysteine-rich activation domains in the yeast Mac1 transcription factor. J Biol Chem 275:29193–29199 [CrossRef]
    [Google Scholar]
  30. Knight S. A., Labbe S., Kwon L. F., Kosman D. J., Thiele D. J. 1996; A widespread transposable element masks expression of a yeast copper transport gene. Genes Dev 10:1917–1929 [CrossRef]
    [Google Scholar]
  31. Knight S. A., Lesuisse E., Stearman R., Klausner R. D., Dancis A. 2002; Reductive iron uptake by Candida albicans: role of copper, iron and the TUP1 regulator. Microbiology 148:29–40
    [Google Scholar]
  32. Labbe S., Zhu Z., Thiele D. J. 1997; Copper-specific transcriptional repression of yeast genes encoding critical components in the copper transport pathway. J Biol Chem 272:15951–15958 [CrossRef]
    [Google Scholar]
  33. Labbe S., Pena M. M., Fernandes A. R., Thiele D. J. 1999; A copper-sensing transcription factor regulates iron uptake genes in Schizosaccharomyces pombe. J Biol Chem 274:36252–36260 [CrossRef]
    [Google Scholar]
  34. Lesuisse E., Simon-Casteras M., Labbe P. 1998; Siderophore-mediated iron uptake in Saccharomyces cerevisiae: the SIT1 gene encodes a ferrioxamine B permease that belongs to the major facilitator superfamily. Microbiology 144:3455–3462 [CrossRef]
    [Google Scholar]
  35. Lin S. J., Pufahl R. A., Dancis A., O'Halloran T. V., Culotta V. C. 1997; A role for the Saccharomyces cerevisiae ATX1 gene in copper trafficking and iron transport. J Biol Chem 272:9215–9220 [CrossRef]
    [Google Scholar]
  36. Linder M. C., Hazegh-Azam M. 1996; Copper biochemistry and molecular biology. Am J Clin Nutr 63:797S–811S
    [Google Scholar]
  37. Mandel M., Higa A. 1970; Calcium dependent bacteriophage DNA infection. J Mol Biol 53:154
    [Google Scholar]
  38. Manns J. M., Mosser D. M., Buckley H. R. 1994; Production of a hemolytic factor by Candida albicans. Infect Immun 62:5154–5156
    [Google Scholar]
  39. Marvin M. E., Williams P. H., Cashmore A. M. 2003; The Candida albicans CTR1 gene encodes a functional copper transporter. Microbiology 149:1461–1474 [CrossRef]
    [Google Scholar]
  40. Moors M. A., Stull T. L., Blank K. J., Buckley H. R., Mosser D. M. 1992; A role for complement receptor-like molecules in iron acquisition by Candida albicans. J Exp Med 175:1643–1651 [CrossRef]
    [Google Scholar]
  41. Morrissey J. A., Williams P. H., Cashmore A. M. 1996; Candida albicans has a cell-associated ferric-reductase activity which is regulated in response to levels of iron and copper. Microbiology 142:485–492 [CrossRef]
    [Google Scholar]
  42. Pufahl R. A., Singer C. P., Peariso K. L., Lin S. J., Schmidt P. J., Fahrni C. J., Culotta V. C., Penner-Hahn J. E., O'Halloran T. V. 1997; Metal ion chaperone function of the soluble Cu(I) receptor Atx1. Science 278:853–856 [CrossRef]
    [Google Scholar]
  43. Ramanan N., Wang Y. 2000; A high-affinity iron permease essential for Candida albicans virulence. Science 288:1062–1064 [CrossRef]
    [Google Scholar]
  44. Ratledge C., Dover L. G. 2000; Iron metabolism in pathogenic bacteria. Annu Rev Microbiol 54:881–941 [CrossRef]
    [Google Scholar]
  45. Robertson L. S., Causton H. C., Young R. A., Fink G. R. 2000; The yeast A kinases differentially regulate iron uptake and respiratory function. Proc Natl Acad Sci U S A 97:5984–5988 [CrossRef]
    [Google Scholar]
  46. Schmitt M. E., Brown T. A., Trumpower B. L. 1990; A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae. Nucleic Acids Res 18:3091–3092 [CrossRef]
    [Google Scholar]
  47. Sherman F., Fink G. R., Hicks J. B. 1986 Laboratory Course Manual for Methods in Yeast Genetics Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
  48. Sonneborn A., Bockmuhl D. P., Gerads M., Kurpanek K., Sanglard D., Ernst J. F. 2000; Protein kinase A encoded by TPK2 regulates dimorphism of Candida albicans. Mol Microbiol 35:386–396 [CrossRef]
    [Google Scholar]
  49. Spizzo T., Byersdorfer C., Duesterhoeft S., Eide D. 1997; The yeast FET5 gene encodes a FET3-related multicopper oxidase implicated in iron transport. Mol Gen Genet 256:547–556
    [Google Scholar]
  50. Szczypka M. S., Thiele D. J. 1989; A cysteine-rich nuclear protein activates yeast metallothionein gene transcription. Mol Cell Biol 9:421–429
    [Google Scholar]
  51. Ward C. G., Bullen J. J. 1999; Clinical and physiological aspects. In Iron and Infection: Molecular, Physiological and Clinical Aspects Edited by Bullen D. J., Griffiths E. Wiley;
    [Google Scholar]
  52. Weissman Z., Shemer R., Kornitzer D. 2002; Deletion of the copper transporter CaCCC2 reveals two distinct pathways for iron acquisition in Candida albicans. Mol Microbiol 44:1551–1560 [CrossRef]
    [Google Scholar]
  53. Wickerham L. J. 1951; Taxonomy of yeast. US Dep Agric Tech Bull 1029:11–59
    [Google Scholar]
  54. Wilson R. B., Davis D., Mitchell A. P. 1999; Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J Bacteriol 181:1868–1874
    [Google Scholar]
  55. Yamaguchi-Iwai Y., Serpe M., Haile D., Yang W., Kosman D. J., Klausner R. D., Dancis A. 1997; Homeostatic regulation of copper uptake in yeast via direct binding of MAC1 protein to upstream regulatory sequences of FRE1 and CTR1. J Biol Chem 272:17711–17718 [CrossRef]
    [Google Scholar]
  56. Yuan D. S., Stearman R., Dancis A., Dunn T., Beeler T., Klausner R. D. 1995; The Menkes/Wilson disease gene homologue in yeast provides copper to a ceruloplasmin-like oxidase required for iron uptake. Proc Natl Acad Sci U S A 92:2632–2636 [CrossRef]
    [Google Scholar]
  57. Yun C. W., Ferea T., Rashford J., Ardon O., Brown P. O., Botstein D., Kaplan J., Philpott C. C. 2000a; Desferrioxamine-mediated iron uptake in Saccharomyces cerevisiae. Evidence for two pathways of iron uptake. J Biol Chem 275:10709–10715 [CrossRef]
    [Google Scholar]
  58. Yun C. W., Tiedeman J. S., Moore R. E., Philpott C. C. 2000b; Siderophore-iron uptake in Saccharomyces cerevisiae. Identification of ferrichrome and fusarinine transporters. J Biol Chem 275:16354–16359 [CrossRef]
    [Google Scholar]
  59. Zhou P. B., Thiele D. J. 1991; Isolation of a metal-activated transcription factor gene from Candida glabrata by complementation in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 88:6112–6116 [CrossRef]
    [Google Scholar]
  60. Zhu Z., Labbe S., Pena M. M., Thiele D. J. 1998; Copper differentially regulates the activity and degradation of yeast Mac1 transcription factor. J Biol Chem 273:1277–1280 [CrossRef]
    [Google Scholar]
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